A laboratory micro‑CT technique is useful to visualize and characterize dermal skin components in a 3D manner

Bowel and skin biopsies from patients with gastrointestinal disorders have revealed neuropathic changes and altered connective tissue. Patients with postural orthostatic tachycardia syndrome (POTS) often suffer from gastrointestinal symptoms and concomitant hypermobility spectrum disorders, such as hypermobile Ehlers-Danlos syndrome (hEDS). Since the skin is more accessible than the bowel, the aim of the present study was to evaluate skin biopsies in a 3D manner using micro-CT in patients with POTS and controls and relate the findings to symptoms presented. Healthy controls (n=13) and patients with POTS with (n=11) or without hEDS/EDS (n=26) were evaluated. Skin biopsies were taken proximally to the lateral malleolus using a 3 mm needle, fixed in formaldehyde and embedded in paraffin. The samples were harvested using a 1.5 mm punch (length, 2-5 mm) and scanned using a laboratory X-ray phase-contrast micro-CT. Scans were evaluated in a blinded manner and the regularity, thickness and tightness of collagen fiber bundles were assessed. All dermal structures were visible without staining. Intraepidermal nerves were not visible and a number of cell types could not be separated. The percentage of disorganized collagen bundles differed between groups, due to the majority being disorganized in hEDS/EDS (P=0.030). The proportion of any disorganized and parallel bundles throughout the biopsy differed within both patient groups (P<0.001) but not within the control group (P=0.175). There were no differences in symptoms between participants with disorganized bundles and participants without disorganized bundles. In conclusion, X-ray phase-contrast micro-CT was suitable to visualize and characterize dermal skin components in 3D. Patients with POTS and hEDS/EDS exhibited more disorganized collagen bundles; however, the technique cannot currently be used for diagnostic purposes until more patients are examined.